To evaluate the genetic hazard of chemicals in our environment and understand their mode of action, it is necessary to place chemical mutagenesis on a quantitative basis in a eukaryote organism that can be thoroughly and economically analyzed genetically. The monofunctional alkylating agent ethyl methanesulfonate (EMS) was selected as the mutagen for developing a model test system because of its known mutagenic effectiveness and its simple chemical structure which makes it relatively easy to synthesize with radionuclides having high specific activity. To place the dosage of EMS on a quantitative basis total alkylation of DNA in Drosophila melanogaster spermatozoa is measured on a per sperm cell basis and then further divided into alkylation at specific sites such as the 7 position of guanine. This dosimetry will then permit the construction of dosage response curves with the dose in terms of alkylation and the response in terms of the extensive mutational spectrum developed with Drosophila. The dose response curve can be used to distinguish among theories for mode of action of a mutagen and is particularly important in extrapolating the genetic effects to a low dose level. Proper determination of dose should provide a basis for comparison among differet species thereby permitting the comparison of the effect of model mutagens among different species. This type of study of comparative mutagenesis is essential in validating our ability to extrapolate among different species and thereby with confidence to extrapolate from test systems to man. The importance of distinguishing between dose to the germ line and exposure of the whole organism is seen in our current results which have shown a nonlinear relationship between dose in terms of alkylated sperm cell DNA and exposure in terms of concentration of the feeding medium. BIBLIOGRAPHIC REFERENCES: Lee, W. R. "Comparison of the mutagenic effects of chemicals and ionizing radiation using Drosophila melanogaster test systems" in Radiation Research, Biomedical, Chemical and Physical Perspectives, (O.F. Nygaard, H.I. Adler and W.K. Sinclair, Eds.), pp. 976-983. Academic Press, New York, 1975. Aaron, C.S. and W.R. Lee, Computerized liquid scintillation counting data management. 1. Time sequence for decay correction: A key for data stoarage and retrieval. Analy. Biochem. 65:573-577 (1975).